The objectives of this investigation is to further define the normal development of the T-lymphocyte system both in terms of its effector functions (proliferation, cytotoxicity, lymphokine synthesis) and its regulatory functions (activation of B-cell antibody synthesis, suppressor and helper T-cell subpopulation and function, and interaction with the monocyte system. We shall then investigate the abnormalities of this system in immaturity and neonatal disorders, in intrauterine and postnatal malnutrition,and in immediate hypersensitivity disorders. The mechanisms of aberration of these systems will be explored by search of abnormal suppression activity, unusual cell-cell interaction and biochemical derangements associated with T-cell dysfunction. Special methods involved in these studies include T-lymphocyte subset T mu and T gamma enumeration, T-suppressor and T-helper functional asssays, lymphokine assays interferon, migration inhibition factor, lymphocyte derived chemotactic factor, and lymphotoxin) T-cell cytotoxicity assays, in vitro IgE synthesis, basophile-bound IgE, and measurements of leukocyte histamine content and release. Studies in immaturity will delineate normal development of suppressor and helper T-cell function, ontogeny of T-cell cytotoxcity and lymphokine production, and T-cell-macrophage interaction. Studies in malnutrition will further define permanent and transient T-cell defects in intrauterine and postnatal malnutrition (including the mechanisms of the marked T-cell depletion in malnutrition), the frequency of T-cell defects in malnourished hospitalized and iron-deficient U.S. children, and the associated biochemical mechanisms involved. Studies in immediate hypersensitivity will delineate normal development and control of mediator production and release and IgE synthesis, aberrations of these systems in infants at risk for allergy, and aberrations in children with hyper IgE immunodeficiency syndromes.